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Snapshots of Life: Fish Awash in Color

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Skin cells from a genetically engineered zebrafish

Credit: Chen-Hui Chen, Duke University

If this image makes you think of a modern art, you’re not alone. But what you’re actually seeing are hundreds of live cells from a tiny bit (0.0003348 square inches) of skin on the tail fin of a genetically engineered adult zebrafish. Zebrafish are normally found in tropical freshwater and are a favorite research model to study vertebrate development and tissue regeneration. The cells have been labeled with a cool, new fluorescent imaging tool called Skinbow. It uniquely color codes cells by getting them to express genes encoding red, green, and blue fluorescent proteins at levels that are randomly determined. The different ratios of these colorful proteins mix to give each cell a distinctive hue when imaged under a microscope. Here, you can see more than 70 detectable Skinbow colors that make individual cells as visually distinct from one another as jellybeans in a jar.

Skinbow is the creation of NIH-supported scientists Chen-Hui Chen and Kenneth Poss at Duke University, Durham, NC, with imaging computational help from collaborators Stefano Di Talia and Alberto Puliafito. As reported recently in the journal Developmental Cell [1], Skinbow’s distinctive spectrum of color occurs primarily in the outermost part of the skin in a layer of non-dividing epithelial cells. Using Skinbow, Poss and colleagues tracked these epithelial cells, individually and as a group, over their entire 2 to 3 week lifespans in the zebrafish. This gave them an unprecedented opportunity to track the cellular dynamics of wound healing or the regeneration of lost tissue over time. While Skinbow only works in zebrafish for now, in theory, it could be adapted to mice and maybe even humans to study skin and possibly other organs.

Snapshots of Life: Cell Skeleton on the Move

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Credit: Torsten Wittmann, University of California, San Francisco

Cells are constantly on the move. They shift, grow, and migrate to new locations—for example, to heal a wound or to intercept an infectious agent as part of an immune response. But how do cells actually move?

In this image, Torsten Wittmann, an NIH-funded cell biologist at the University of California, San Francisco, reveals the usually-invisible cytoskeleton of a normal human skin cell that lends the cell its mobility. The cytoskeleton is made from protein structures called microtubules—the wispy threads surrounding the purple DNA-containing nucleus—and filaments of a protein called actin, seen here as the fine blue meshwork in the cell periphery. Both actin and microtubules are critical for growth and movement.

Cool Videos: Metabolomics

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Metabolomics video screenshot

Today’s feature in my Cool Video series is a scientific film noir from the University of Florida in Gainesville. Channeling Humphrey Bogart’s hard-boiled approach to detective work, the protagonist of this video is tracking down metabolites—molecules involved in biological mysteries with more twists and turns than “The Maltese Falcon.”

If you’d like a few more details before or after watching the video, here’s how the scientists themselves describe their project: “Inside our cells, chemical heroes, victims, and villains leave behind clues about our health. Meet Dr. Art Edison, one of many metabolomics PIs who are on the case. Their quest? To tail and fingerprint small molecules, called metabolites, which result from the chemical processes that fuel and sustain life. Metabolites can shed light on the state of health, nutrition, or disease in a living thing—whether human, animal, or plant. Funded by National Institutes of Health grant U24DK097209, the University of Florida Southeast Center for Integrated Metabolomics is sleuthing through these cellular secrets.”

Snapshots of Life: Wild Outcome from Knocking Out Mobility Proteins

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Spiky fibroblast cell

Credit: Praveen Suraneni and Rong Li, Stowers Institute for Medical Research

When biologists disabled proteins critical for cell movement, the result was dramatic. The membrane, normally a smooth surface enveloping the cell, erupted in spiky projections. This image, which is part of the Life: Magnified exhibit, resembles a supernova. Although it looks like it exploded, the cell pictured is still alive.

To create the image, Rong Li and Praveen Suraneni, NIH-funded cell biologists at the Stowers Institute for Medical Research in Kansas City, Missouri, disrupted two proteins essential to movement in fibroblasts—connective tissue cells that are also important for healing wounds. The first, called ARPC3, is a protein in the Arp2/3 complex. Without it, the cell moves more slowly and randomly [1]. Inhibiting the second protein gave this cell its spiky appearance. Called myosin IIA (green in the image), it’s like the cell’s muscle, and it’s critical for movement. The blue color is DNA; the red represents a protein called F-actin.

This SWELL Protein Keeps Cells in Shape

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Human cell

Caption: A human cell expressing both the SWELL1 (red) and green fluorescent protein. The red dots reveal the location of SWELL1 on the cell surface.
Credit: Zhaozhu Qiu, The Scripps Research Institute, La Jolla, CA

Anyone who’s taken part in a water balloon fight knows what happens when you fill a balloon with too much water—it bursts. Now, consider that most of our cells are essentially water balloons: a thin membrane envelope containing a mixture that’s mostly water along with some salts, proteins, lipids, carbohydrates, and nucleic acids. Given that the average adult’s body is about 60% water, what keeps our cells from overfilling and exploding?

A few years ago, Zhaozhu Qiu, a postdoctoral fellow in Ardem Patapoutian’s lab at Scripps Research Institute in La Jolla, CA, decided to dig into the molecular details of how cells are able to sense their volume and adjust their shapes accordingly. It’s long been known that, when cells are placed in low-salt solutions, water tends to flow into them, causing them to swell—sometimes to the verge of bursting. Scientists determined, about 30 years ago, that, when this occurs, channels in the cell membrane open and the cells release chloride and other molecules, such as amino acids: a process that drives out the excess water and returns cells to their normal size [1].

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